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Ghrelin receptors mediate ghrelin-induced excitation of agouti-related protein/neuropeptide Y but not pro-opiomelanocortin neurons.
- Source :
-
Journal of neurochemistry [J Neurochem] 2017 Aug; Vol. 142 (4), pp. 512-520. Date of Electronic Publication: 2017 Jun 21. - Publication Year :
- 2017
-
Abstract
- Ghrelin increases food intake and body weight by stimulating orexigenic agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons and inhibiting anorexic pro-opiomelanocortin (POMC) neurons in the hypothalamus. Growth hormone secretagogue receptor (Ghsr) mediates the effect of ghrelin on feeding behavior and energy homeostasis. However, the role of Ghsr in the ghrelin effect on these two populations of neurons is unclear. We hypothesized that Ghsr mediates the effect of ghrelin on AgRP and POMC neurons. In this study, we determined whether Ghsr similarly mediates the effects of ghrelin on AgRP/NPY and POMC neurons using cell type-specific Ghsr-knockout mice. Perforated whole-cell recordings were performed on green fluorescent protein-tagged AgRP/NPY and POMC neurons in the arcuate nucleus in hypothalamic slices. In Ghsr <superscript>+/+</superscript> mice, ghrelin (100 nM) significantly increased the firing activity of AgRP/NPY neurons but inhibited the firing activity of POMC neurons. In Ghsr <superscript>-/-</superscript> mice, the excitatory effect of ghrelin on AgRP/NPY neurons was abolished. Ablation of Ghsr also eliminated ghrelin-induced increases in the frequency of GABAergic inhibitory postsynaptic currents of POMC neurons. Strikingly, ablation of Ghsr converted the ghrelin effect on POMC neurons from inhibition to excitation. Des-acylated ghrelin had no such effect on POMC neurons in Ghsr <superscript>-/-</superscript> mice. In both Ghsr <superscript>+/+</superscript> and Ghsr <superscript>-/-</superscript> mice, blocking GABA <subscript>A</subscript> receptors with gabazine increased the basal firing activity of POMC neurons, and ghrelin further increased the firing activity of POMC neurons in the presence of gabazine. Our findings provide unequivocal evidence that Ghsr is essential for ghrelin-induced excitation of AgRP/NPY neurons. However, ghrelin excites POMC neurons through an unidentified mechanism that is distinct from conventional Ghsr.<br /> (© 2017 International Society for Neurochemistry.)
- Subjects :
- Agouti-Related Protein metabolism
Animals
Arcuate Nucleus of Hypothalamus metabolism
Eating drug effects
Mice, Transgenic
Neurons drug effects
Patch-Clamp Techniques methods
Pro-Opiomelanocortin metabolism
Ghrelin pharmacology
Hypothalamus metabolism
Neurons metabolism
Neuropeptide Y metabolism
Receptors, Ghrelin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 142
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28547758
- Full Text :
- https://doi.org/10.1111/jnc.14080